UC Riverside-led rat study finds an immune receptor in the hippocampus is responsible for the onset of the disease after brain injuries
A research team led by a scientist at the University of California, Riverside, has found that brain treated with certain drugs within a few days of an injury have a dramatically reduced risk of developing epilepsy later in life.
The development of epilepsy is a major clinical complication after brain injury, and the disease can often take years to appear.
“Working on rats, whose immune response system models that of humans, we identified that after brain injury a certain immune system receptor makes the brain more excitable, which promotes development of epilepsy,” said Viji Santhakumar, an associate professor of molecular, cell, and systems biology at UC Riverside and the lead author of the study that appears in the Annals of Neurobiology. “If this receptor can be suppressed, preferably within a day after injury, the future development of epilepsy can be reduced if not entirely prevented.”
The receptor in question is the Toll-like receptor 4, or TLR4, an innate immune receptor. Following a brain injury, TLR4 increases excitability in the dentate gyrus of the hippocampus, the brain structure that plays a major role in learning and memory.
“What our rat studies on traumatic brain injury show is that if we target early changes in excitability, we can alter long-term pathology,” Santhakumar said. “Blocking TLR4 signaling shortly after brain injury reduces neuronal excitability in the hippocampus and seizure susceptibility. This seizure susceptibility is not reduced if we delay the blocking of TLR4 signaling after injury.”
Paradoxically, Santhakumar’s team found that drugs such as Resatorvid, which block TLR4 in the injured brain, caused epilepsy in uninjured brains.
“This paradox is difficult to understand,” Santhakumar said. “We are currently looking at molecular signaling pathways in injured and uninjured brains to make sense of it.”